Nicotine stimulates the expression of cyclooxygenase-2 mRNA via NFkappaB activation in human gingival fibroblasts.

Nicotine, a major component in tobacco smoke, stimulates the synthesis of prostaglandin E(2). We investigated the involvement of the transcription nuclear factor kappa B (NFkappaB) in the nicotine-induced expression of cyclooxygenase-2 (COX-2), a key enzyme for prostaglandin synthesis, in human gingival fibroblasts. Nicotine-stimulated release of prostaglandin E(2) and expression of COX-2 mRNA in a time- and dose-dependent manner. The nicotine-stimulated release of prostaglandin E(2) and expression of COX-2 mRNA and protein were inhibited by an NFkappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), by approximately 50%. Nicotine stimulation of IkappaBalpha, an inhibitor of NFkappaB degradation, was also characterized by Western blotting. Mecamylamine, a specific antagonist of the nicotinic acetylcholine receptor, failed to inhibit the effect of nicotine on prostaglandin E(2) release. When human gingival fibroblasts were incubated with [3H]-nicotine, uptake of nicotine was observed. These results suggest that nicotine is taken up by human gingival fibroblasts and that it then stimulates COX-2 expression via the activation of NFkappaB and the subsequent release of prostaglandin E(2).